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Objective::To explore the protective effect of Huoxue Dingtong prescription on myocardial ischemia reperfusion injury in animal model based on nuclear transcription factor-κB(NF-κB) signal pathway. Method::In compound Danshen dropping pill group, SD rats were randomly divided into sham group, model group, compound salvia miltiorrhiza dropping pill group, high-dose Huoxue Dingtong group low-dose Huoxue Dingtong group, high-dose Huoxue Dingtong+ NF-κB inhibitor group. The rats in each group were administered continuously for 2 weeks. The rats in high-dose Huoxue Dingtong group+ pyrrolidine dithiocarbamate(PDTC) group were intraperitoneally administered the next day after modeling. Injection with PDTC and ligation of anterior descending branch of left coronary artery were performed to detect left ventricular function and Na+ -K+ -ATPase activity. Blood was collected from each animal abdominal aorta, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum creatine kinase isoenzyme (CK-MB), troponin T (cTnT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), superoxide gasification enzyme (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px). Western blot was used to detect the expressions of NF-κB, NF-κB inhibitor α (IκBα) and IκB kinase(IκκB) in myocardium. Result::Compared with model group, compound Danshen dropping pill group, high-dose Huoxue Dingtong group and low-dose Huoxue Dingtong group could reduce serum CK-MB, cTnT, TNF-α, IL-6, IL-1β, MDA, increase SOD and GSH-Px contents, increase the protein expressions of IκBα and IκB in myocardial tissue, and increase the activity of Na+ -K+ -ATPase in myocardial energy metabolism in myocardial ischemia-reperfusion model rats (P<0.05). However, high-dose Huoxue Dingtong group+ PDTC did not decrease serum CK-MB, cTnT, TNF-α, IL-6, IL-1β and MDA, increase SOD, GSH-Px, and increase the protein expression levels of IκBα and IκκB in myocardial tissue. There was no significant difference between high-dose Huoxue Dingtong group+ PDTC and model group. Conclusion::Huoxue Dingtang prescription can inhibit the activation of NF-κB signaling pathway, reduce the expression of inflammatory mediators and the production of free radicals, and increase the activity of Na+ -K+ -ATPase in the process of myocardial energy metabolism by up-regulating the expressions of IκBα and IκκB proteins in myocardial tissue of myocardial ischemia-reperfusion model.
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OBJECTIVE: To investigate the feasibility and safety of simultaneous liver section combined with pulmonary wedge resection via the trans-diaphragmatic approach in patients of synchronous liver and lung metastases. METHODS: The clinical data of 3 patients of synchronous liver and lung metastases who underwent simultaneous liver section combined with pulmonary wedge resection via the trans-diaphragmatic approach at Peking University Cancer Hospital between May 2017 and June 2017 were retrospectively analyzed. RESULTS: All liver and lung metastases of 3 patients were successfully resected. Operation time for liver resections were 82, 50 and 43 min, while blood losses were 400, 150 and 200 mL respectively. Meanwhile, operation time for pulmonary resections were 45, 60 and 36 min, and blood losses were 10, 30 and 5 mL respectively. Neither perioperative death nor severe complication occurred. CONCLUSION: Simultaneous liver resection combined with pulmonary wedge resection via the trans-diaphragmatic approach is a safe technique for the patients with resectable synchronous liver and lung metastases
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<p><b>OBJECTIVE</b>To explore the biological mechanisms underlying Angelica sindsis polysaccharide (ASP) -induced aging of human-derived leukemia stem cells (LSCs) in vitro.</p><p><b>METHOD</b>Acute myelogenous leukemia stem cells were isolated by magnetic activated cell sorting (MACS). The ability of LSC proliferation treated by various concentration of ASP(20-80 mg · L(-1)) in vitro for 48 hours were tested using cell counting Kit-8 ( CCK8) , colony forming were evaluated by methylcellulose CFU assay. The ultra structure changes of AML CD34+ CD38- cells were analyzed by transmission electron microscopy. The aging cells were detected with senescence-β-galactosidase Kit staining. Expression of aging-related p53, p21, p16, Rb mRNA and P16, Rb, CDK4 and Cyclin E protein were detected by quantitative reverse transcription polymerase chain reaction( qRT-PCR) and Western blotting, respectively.</p><p><b>RESULT</b>The purity of the CD34 + CD38 - cells is (91.15 ± 2.41)% after sorted and showed good morphology. The proliferation of LSC was exhibited significantly concentration-dependent inhibited after exposure to various concentration of ASP. Treated by 40 mg · L(-1) ASP for 48 hours, the percentage of positive cells stained by SA-β-Gal was dramatically increased (P < 0.01) and the colony-formed ability has been weakened (P < 0.01). The observation of ultrastructure showed that cell heterochromatin condensation and fragmentation, mitochondrial swelling, lysosomes increased in number. Aging-related p53, p21, p16, Rb and P16, Rb were up-regulated, protein regulatory cell-cycle CDK4 and Cyclin E were down-regulated. ASP may induce the senescence of LSCs effectively in vitro, P16-Rb cell signaling pathway play a significant role in this process.</p><p><b>CONCLUSION</b>ASP can induce human leukemia stem cell senescence in vitro, the mechanism involved may be related to ASP regulation P16-Rb signaling pathways.</p>
Subject(s)
Humans , Angelica sinensis , Chemistry , Cell Cycle , Cell Cycle Proteins , Genetics , Metabolism , Cells, Cultured , Cellular Senescence , Drugs, Chinese Herbal , Pharmacology , Gene Expression Regulation, Leukemic , Leukemia , Drug Therapy , Genetics , Metabolism , Neoplastic Stem Cells , Cell Biology , Polysaccharides , Pharmacology , Signal TransductionABSTRACT
Objective: To investigate the mechanisms on the regulation of telomere and telomerase in the process of senescence induction of human-derived CD34+CD38- leukemia stem cells (LSC) subpopulation by Angelica sinensis polysaccharide (ASP). Methods: The human-derived CD34+CD38- LSC subpopulation was isolated from acute myelogenous leukemia bone marrow mononuclear cells by magnetic activated cell sorting. The inhibition of ASP on CD34+CD38- LSC subpopulation proliferation was detected by CCK-8 assay. The percentage of senescent cells was detected by SA-β-Gal staining. The colony-formed ability was detected by Colony-forming Assay. The levels of telomerase activities and telomerase reverse transcriptase (TERT) gene expression were performed by TRAP-PCR and quantitative RT-PCR, respectively. The changes of telomere length were tested by Southern blotting assay. Results: The CD34+CD38- LSC subpopulation could be effectively isolated by MACS. The purity of CD34+CD38- LSC population is up to (91.15 ± 2.41)%; The cells showed the features of well-stacked morphology, high transparency, well refraction under inverted phase contrast microscope. ASP had a remarkable dose-dependent inhibition on CD34+CD38- LSC proliferation in vitro culture (P < 0.05). The number of SA-β-Gal staining positive cells had been increased compared to the cells in control group (P < 0.01), a decrease in colony-forming abilities (P < 0.01), a decrease level on TERT gene and telomerase activities (P < 0.05), and a shorter length on telomere of CD34+CD38- LSC after 40 μg/mL ASP co-culture for 48 h (P < 0.05). Conclusion: ASP could induce the senescence of human derived leukemia bone marrow CD34+CD38- LSC via regulating the cell telomere system in vitro co-culture.
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Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in section of brain tissue decreased, the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in hippocampus decreased, the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group, the spatial learning and memory capacities were enhanced in Rg1 normal group, SA-beta-Gal positive granules in section of brain tissue decreased in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability, regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.